Bacteria

Viruses

Cancer

Our Portfolio of Therapies

We have generated a pipeline of 5 human-derived therapeutics across infectious diseases (bacterial, viral) and cancer indications, each with demonstrated experimental efficacy.

The first of our therapeutics will reach Phase I clinical trials by 2018.

Bacteria

Broad-Spectrum Biofilm Disruptor Human mAb, TRL1068

Biofilm protects bacteria from antibiotics resulting in antibiotic resistance.



Increasing antibiotic resistance is a global problem and biofilm presence is a common motif in antibiotic-resistant infections



~60-80% of chronic infections involve biofilm, resulting in a $25B US annual cost



Indications include: Infective endocarditis, osteomyelitis, diabetic foot infections, Lyme disease, cystic fibrosis, and many others

TRL1068 is broad-spectrum, disrupting biofilm across multiple bacteria species




Upon biofilm disruption, bacteria regain antibiotic susceptibility

Trellis has demonstrated in animal models the potency of TRL1068 in combination with antibiotics to overcome antibiotic resistance

Treatment with TRL1068 in combination with daptomycin improved recovery and survival rates in MRSA-infected mice.

TRL1068 increases efficacy of daptomycin (DAP), decreasing the number of planktonic (non-biofilm) bacteria by 100-fold.

For biofilm-adherent bacteria, TRL1068 when combined with daptomycin (DAP) results in 1000-fold reduction of bacteria compared to DAP alone

Viruses

Cytomegalovirus (CMV) Human mAb, TRL345

Cytomegalovirus (CMV) is carried by more than half of the population and is the leading cause of serious complications in transplant recipients (affecting 60-70%).



In non-carriers, a CMV infection is a leading non-genetic cause of birth defects such as hearing loss, visual deficits, and cognitive delays



CMV costs the US $1B annually

Seroprevalence shaded in blues. Congenital CMV denoted by colored circles
(Source: “’The Silent’ Global Burden of Congenital Cytomegalovirus.”
http://cmr.asm.org/content/26/1/86/F7.expansion.html)

TRL345 demonstrates greater efficacy than alternatives in in vitro experiments

For fetal-maternal indication, TRL345 protected all cell types that are targets for the virus.




In addition, TRL345 demonstrated 10-fold potency advantage over Cytotect’s Hyperimmunoglobulin (HIG), even at 10-100-fold lower concentrations.

Viruses

Pan-influenza Human mAb, CF404 - Licensed to Contrafect Corporation, Inc.

Each year, 5-10% of the US population acquire the flu virus, costing the US $10.4B a year in direct medical expenses (Source: CDC).



On average, more than 200,000 patients within the US are hospitalized each year for seasonal influenza-associated infections.



In 2015, the CDC estimated that influenza vaccination prevented ~67K influenza-associated hospitalizations, but only ~50% of immunized elderly respond to the vaccine and produce neutralizing antibodies



Emerging pandemic strains, such as the 2009 avian flu which infected 1 billion of the world’s population, remain a threat.

CF404, a monoclonal antibody cocktail against influenza A and B, is more efficacious post-infection as well as against emerging strains than Tamiflu, the most common anti-influenza drug

CF404 targets a region of the virus that is highly conserved across multiple influenza strains. This suggests potential efficacy against emergent mutant strains

Tamiflu efficacy drops sharply when given more than 24 hours post-infection. CF404 is still highly effective even when given 96 hours post-infection.

Viruses

Respiratory Syncytial Virus (RSV) Human mAb, TRL3D3

Respiratory Syncytial Virus (RSV) infects nearly all children worldwide by 2 to 3 years of age.



3-7% of children under the age of 2 are hospitalized annually in the US.



Globally, it is a leading cause of lower respiratory tract disease leading to 200,000 deaths and 3 million hospitalizations of young children annually

The currently available antibody treatment, palivizumab (Synagis), must be administered before infection.

In animal models, TRL3D3, demonstrated 100-fold greater efficacy than palivizumab, even when administered post-infection.

TRL3D3 is more effective at viral inhibition, demonstrated through greater restoration of normal airway function (indicated by lowered airway resistance above) relative to Synagis, even 14 days after infection.

Viruses

Immune Checkpoint Modulators (ICMs) and Tumor-Associated Antigens (TAAs)

Cancer is the second most common cause of death in the United States, accounting for nearly 1 in 4 deaths, 595,000 deaths estimated in 2016 (American Cancer Society).

Most Lethal Types:
- Lung and bronchial
- Colorectal
- Pancreatic
- Breast
- Liver and intrahepatic bile duct
- Prostate

Cancer Incidence Rates by State, 2008-2012 (all cancer types, per 100,000)

Sources: American Cancer Society. https://cancerstatisticscenter.cancer.org; North American Association of Central Cancer Registries (NAACCR), 2015. http://www.naaccr.org/DataandPublications/CINAPubs.aspx

Trellis antibodies fight cancer through two methods:

Immune Checkpoint Modulators (ICMs)

One of the methods in which cancer proliferates is through the supression of the patient’s immune system via immune checkpoint modulators (ICMs).

Anti-ICM antibodies blocking the PD-1/PD-L1 interaction between T Cells and cancer cells have demonstrated great success against multiple types of cancer in clinical trials.

However, anti-PD-1/anti-PD-L1 antibodies do not cover the entire breadth of cancer types. Fully successful treatment will likely require multiple anti-ICM antibodies which offer a robust immune checkpoint blockade, in combination with other methods.

Trellis antibodies, Anti-KIR and Anti-TIM3 mAbs target novel receptors implicated in the immune checkpoint interaction and aid stimulation of the natural immune system, thereby improving the body’s natural ability to fight cancer.

Tumor-Associated Antigens (TAAs)

Other Trellis antibodies target TAAs, like TRL10001 that recognizes the extracellular domain of Anaplastic Lymphoma Kinase (ALK).

ALK plays a role during the development of the nervous system and is associated to many cancers including lung, thyroid and many brain tumors, while is not present in normal tissues.

TRL10001 is high affinity (100pM) human antibody that rapidly internalizes in neuroblastoma cells, which makes it an ideal candidate for an Antibody Drug Conjugate.

Antibodies, including our Anti-ALK candidate, which target tumor-associated antigens, may function as antibody conjugates and therefore be coupled with small molecule drug treatments. Due to the antibody specificity, the coupled conjugates can deliver concentrated doses of the drug directly to the tumor cell, minimizing side effects by sparing healthy tissue.

In vitro pulse-chase experiment:
Trellis anti-ALK mAb, TRL10001, bound to ALK-expressing cells and was internalized within 30 minutes.

Frequencies of memory B-cells specific for ICMs are very low (single digits per 105 B-cells) but Trellis has found and cloned high affinity antibodies to several ICMs: KIR, TIM-3 B7-H3, LAG-3 and CEACAM1:

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